Recent observations in endothelial cells and macrophages indicate that nicotinic acetylcholine receptors (nAChRs) are potential novel players in mechanisms linked to atherogenesis. In macrophages, α7nAChR mediates anti‐inflammatory actions and contributes to regulation of cholesterol flux and phagocytosis. Considering that macrophage apoptosis is a key process throughout all stages of atherosclerotic lesion development, in the present study, we examined for the first time the impact of α7nAChR expression and function in macrophage survival and apoptosis using in vitro polarized (M1 and M2) bone marrow‐derived macrophages (BMDMs) from wild‐type and α7nAChR knockout mice. Our findings show that stimulation of α7nAChR results in activation of the STAT3 prosurvival pathway and protection of macrophages from endoplasmic reticulum (ER) stress‐induced apoptosis. These actions are rather selective for M2 BMDMs and are associated to activation of the JAK2/STAT3 axis. Remarkably, these effects are completely lost in M2 macrophages lacking α7nAChR.